Janus kinase 1 explained

JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family (e.g. IL-2R, IL-7R, IL-9R and IL-15R), the IL-4 receptor family (e.g. IL-4R and IL-13R), the gp130 receptor family (e.g. IL-6R, IL-11R, LIF-R, OSM-R, cardiotrophin-1 receptor (CT-1R), ciliary neurotrophic factor receptor (CNTF-R), neurotrophin-1 receptor (NNT-1R) and Leptin-R). It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors.^[1] Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. Loss of Jak1 is lethal in neonatal mice, possibly due to difficulties suckling.^[2] Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body.^[3]

Interactions

Janus kinase 1 has been shown to interact with:

• ELP2,^[4]
• GNB2L1^[5]
• IL6ST,^{[6] [7] [8]}
• Grb2,^{[9] [10]}
• IL2RB,^{[11] [12] [13] [14]}
• IRS1,^{[15] [16]}
• IL10RA,^{[17] [18]}
• PTPN11,^{[19] [20]}
• STAM2,^{[21] [22]}
• STAT3,^{[23] [24]}
• STAT5A,^[25]
• STAT5B,^[25] and
• TNFRSF1A.^{[26] [27]}

See also

• Janus kinase inhibitor

Further reading

• Donnelly RP, Dickensheets H, Finbloom DS . The interleukin-10 signal transduction pathway and regulation of gene expression in mononuclear phagocytes . J. Interferon Cytokine Res. . 19 . 6 . 563–73 . 1999 . 10433356 . 10.1089/107999099313695 .
• Carter-Su C, Rui L, Stofega MR . SH2-B and SIRP: JAK2 binding proteins that modulate the actions of growth hormone . Recent Prog. Horm. Res. . 55 . 293–311 . 2000 . 11036942 .
• Kostrodymova GM . [An experimental study of the possible sensitizing properties of triethanolamine contained in chemical compounds used at home] . Gigiena i Sanitariia . 6 . 10–2 . 1976 . 1213395 .
• Howard OM . Characterization of a class 3 tyrosine kinase . Oncogene . 7 . 5 . 895–900 . 1992 . 1373877 . Dean M . Young H . Ramsburg . M . Turpin . JA . Michiel . DF . Kelvin . DJ . Lee . L . Farrar . WL .
• Pritchard MA . Two members of the JAK family of protein tyrosine kinases map to chromosomes 1p31.3 and 9p24 . Mamm. Genome . 3 . 1 . 36–8 . 1992 . 1581631 . 10.1007/BF00355839 . Baker E . Callen DF . Sutherland . Grant R. . Wilks . Andrew F. . 31384629 .
• Wilks AF . Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase . Mol. Cell. Biol. . 11 . 4 . 2057–65 . 1991 . 1848670 . 10.1128/MCB.11.4.2057. 359893 . Harpur AG . Kurban RR . Ralph . SJ . Zürcher . G . Ziemiecki . A .
• Johnston JA . Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases . J. Biol. Chem. . 270 . 48 . 28527–30 . 1996 . 7499365 . 10.1074/jbc.270.48.28527 . Wang LM . Hanson EP . Sun . XJ . White . MF . Oakes . SA . Pierce . JH . O'Shea . JJ . free .
• Nicholson SE . Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine-phosphorylated after receptor activation . Proc. Natl. Acad. Sci. U.S.A. . 91 . 8 . 2985–8 . 1994 . 7512720 . 10.1073/pnas.91.8.2985 . 43499 . Oates AC . Harpur AG . Ziemiecki . A . Wilks . AF . Layton . JE . 1994PNAS...91.2985N . free .
• Domanski P . Homodimerization and intermolecular tyrosine phosphorylation of the Tyk-2 tyrosine kinase . FEBS Lett. . 374 . 3 . 317–22 . 1995 . 7589562 . 10.1016/0014-5793(95)01094-U . Yan H . Witte MM . Krolewski . J . Colamonici . OR . free.
• Modi WS, Farrar WL, Howard OM . Confirmed assignment of a novel human tyrosine kinase gene (JAK1A) to 1p32.3→p31.3 by nonisotopic in situ hybridization . Cytogenet. Cell Genet. . 69 . 3–4 . 232–4 . 1995 . 7698020 . 10.1159/000133971 .
• Miyazaki T . Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits . Science . 266 . 5187 . 1045–7 . 1994 . 7973659 . 10.1126/science.7973659 . Kawahara A . Fujii H . Nakagawa . Y . Minami . Y . Liu . Z. . Oishi . I . Silvennoinen . O . Witthuhn . B. . 1994Sci...266.1045M .
• Müller M . The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction . Nature . 366 . 6451 . 129–35 . 1993 . 8232552 . 10.1038/366129a0 . Briscoe J . Laxton C . Guschin . Dmitry . Ziemiecki . Andrew . Silvennoinen . Olli . Harpur . Ailsa G. . Barbieri . Giovanna . Witthuhn . Bruce A. . 1993Natur.366..129M . 27334189 .
• Lee ST, Strunk KM, Spritz RA . A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes . Oncogene . 8 . 12 . 3403–10 . 1993 . 8247543 .
• Lütticken C . Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130 . Science . 263 . 5143 . 89–92 . 1994 . 8272872 . 10.1126/science.8272872 . Wegenka UM . Yuan J . Buschmann . J . Schindler . C . Ziemiecki . A . Harpur . A. . Wilks . A. . Yasukawa . K . 1994Sci...263...89L .
• Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E . Involvement of Janus kinases in the insulin signaling pathway . Eur. J. Biochem. . 234 . 2 . 656–60 . 1996 . 8536716 . 10.1111/j.1432-1033.1995.656_b.x . free .
• Friedmann MC, Migone TS, Russell SM, Leonard WJ . Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation . Proc. Natl. Acad. Sci. U.S.A. . 93 . 5 . 2077–82 . 1996 . 8700888 . 10.1073/pnas.93.5.2077 . 39912 . 1996PNAS...93.2077F . free .
• Gauzzi MC . Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase . J. Biol. Chem. . 271 . 34 . 20494–500 . 1996 . 8702790 . 10.1074/jbc.271.34.20494 . Velazquez L . McKendry R . Mogensen . KE . Fellous . M . Pellegrini . S . free .
• Demoulin JB . A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9 . Mol. Cell. Biol. . 16 . 9 . 4710–6 . 1996 . 8756628 . 10.1128/MCB.16.9.4710. 231471 . Uyttenhove C . Van Roost E . Delestré . B . Donckers . D . Van Snick . J . Renauld . JC .
• Yin T, Shen R, Feng GS, Yang YC . Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases . J. Biol. Chem. . 272 . 2 . 1032–7 . 1997 . 8995399 . 10.1074/jbc.272.2.1032 . free .
• Bluyssen HA, Levy DE . Stat2 is a transcriptional activator that requires sequence-specific contacts provided by stat1 and p48 for stable interaction with DNA . J. Biol. Chem. . 272 . 7 . 4600–5 . 1997 . 9020188 . 10.1074/jbc.272.7.4600 . free .

Notes and References

1. Gadina M, Hilton D, Johnston JA, Morinobu A, Lighvani A, Zhou YJ, Visconti R, O'Shea JJ . Signaling by type I and II cytokine receptors: ten years after . Curr. Opin. Immunol. . 13 . 3 . 363–73 . 2001 . 11406370 . 10.1016/S0952-7915(00)00228-4.
2. Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, King KL, Sheehan KC, Yin L, Pennica D, Johnson EM, Schreiber RD . Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses . Cell . 93 . 3 . 373–83 . 1998 . 9590172 . 10.1016/S0092-8674(00)81166-6. 18684846 . free .
3. News: Protein JAK Makes Cancer Cells Contract, So They Can Squeeze Out Of A Tumor . Christian Nordqvist. Medical News Today.
4. August 2000 . Collum RG, Brutsaert S, Lee G, Schindler C . A Stat3-interacting protein (StIP1) regulates cytokine signal transduction . Proc. Natl. Acad. Sci. U.S.A. . 97 . 18 . 10120–5 . 10954736 . 27739 . 10.1073/pnas.170192197. 2000PNAS...9710120C . free .
5. September 2003 . Usacheva A, Tian X, Sandoval R, Salvi D, Levy D, Colamonici OR . The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex . J. Immunol. . 171 . 6 . 2989–94 . 12960323 . 10.4049/jimmunol.171.6.2989. free .
6. October 2001 . Haan C, Is'harc H, Hermanns HM, Schmitz-Van De Leur H, Kerr IM, Heinrich PC, Grötzinger J, Behrmann I . Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction . J. Biol. Chem. . 276 . 40 . 37451–8 . 11468294 . 10.1074/jbc.M106135200. free .
7. December 1997 . Kim H, Baumann H . Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells . J. Biol. Chem. . 272 . 49 . 30741–7 . 9388212 . 10.1074/jbc.272.49.30741. free .
8. January 2002 . Haan C, Heinrich PC, Behrmann I . Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation . Biochem. J. . 361 . Pt 1 . 105–11 . 11742534 . 1222284 . 10.1042/0264-6021:3610105.
9. September 2001 . Kim H, Lee YH, Won J, Yun Y . Through induction of juxtaposition and tyrosine kinase activity of Jak1, X-gene product of hepatitis B virus stimulates Ras and the transcriptional activation through AP-1, NF-kappaB, and SRE enhancers . Biochem. Biophys. Res. Commun. . 286 . 5 . 886–94 . 11527382 . 10.1006/bbrc.2001.5496.
10. December 1995 . Giorgetti-Peraldi S, Peyrade F, Baron V, Van Obberghen E . Involvement of Janus kinases in the insulin signaling pathway . Eur. J. Biochem. . 234 . 2 . 656–60 . 8536716 . 10.1111/j.1432-1033.1995.656_b.x. free .
11. November 1994 . Miyazaki T, Kawahara A, Fujii H, Nakagawa Y, Minami Y, Liu ZJ, Oishi I, Silvennoinen O, Witthuhn BA, Ihle JN . Functional activation of Jak1 and Jak3 by selective association with IL-2 receptor subunits . Science . 266 . 5187 . 1045–7 . 7973659 . 10.1126/science.7973659. 1994Sci...266.1045M .
12. November 1994 . Russell SM, Johnston JA, Noguchi M, Kawamura M, Bacon CM, Friedmann M, Berg M, McVicar DW, Witthuhn BA, Silvennoinen O . Interaction of IL-2R beta and gamma c chains with Jak1 and Jak3: implications for XSCID and XCID . Science . 266 . 5187 . 1042–5 . 7973658 . 10.1126/science.7973658. 1994Sci...266.1042R .
13. April 1998 . Zhu MH, Berry JA, Russell SM, Leonard WJ . Delineation of the regions of interleukin-2 (IL-2) receptor beta chain important for association of Jak1 and Jak3. Jak1-independent functional recruitment of Jak3 to Il-2Rbeta . J. Biol. Chem. . 273 . 17 . 10719–25 . 9553136 . 10.1074/jbc.273.17.10719. free .
14. November 1998 . Migone TS, Rodig S, Cacalano NA, Berg M, Schreiber RD, Leonard WJ . Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and phosphorylation . Mol. Cell. Biol. . 18 . 11 . 6416–22 . 9774657 . 109227 . 10.1128/mcb.18.11.6416.
15. March 1998 . Gual P, Baron V, Lequoy V, Van Obberghen E . Interaction of Janus kinases JAK-1 and JAK-2 with the insulin receptor and the insulin-like growth factor-1 receptor . Endocrinology . 139 . 3 . 884–93 . 9492017 . 10.1210/endo.139.3.5829. free .
16. December 1995 . Johnston JA, Wang LM, Hanson EP, Sun XJ, White MF, Oakes SA, Pierce JH, O'Shea JJ . Interleukins 2, 4, 7, and 15 stimulate tyrosine phosphorylation of insulin receptor substrates 1 and 2 in T cells. Potential role of JAK kinases . J. Biol. Chem. . 270 . 48 . 28527–30 . 7499365 . 10.1074/jbc.270.48.28527. free .
17. August 2002 . Usacheva A, Kotenko S, Witte MM, Colamonici OR . Two distinct domains within the N-terminal region of Janus kinase 1 interact with cytokine receptors . J. Immunol. . 169 . 3 . 1302–8 . 12133952 . 10.4049/jimmunol.169.3.1302. free .
18. December 2002 . Usacheva A, Sandoval R, Domanski P, Kotenko SV, Nelms K, Goldsmith MA, Colamonici OR . Contribution of the Box 1 and Box 2 motifs of cytokine receptors to Jak1 association and activation . J. Biol. Chem. . 277 . 50 . 48220–6 . 12374810 . 10.1074/jbc.M205757200. free .
19. January 1997 . Yin T, Shen R, Feng GS, Yang YC . Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases . J. Biol. Chem. . 272 . 2 . 1032–7 . 8995399 . 10.1074/jbc.272.2.1032. free .
20. January 2003 . Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG, Heinrich PC, Schaper F . SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130 . J. Biol. Chem. . 278 . 1 . 661–71 . 12403768 . 10.1074/jbc.M210552200. free .
21. December 2000 . Pandey A, Fernandez MM, Steen H, Blagoev B, Nielsen MM, Roche S, Mann M, Lodish HF . Identification of a novel immunoreceptor tyrosine-based activation motif-containing molecule, STAM2, by mass spectrometry and its involvement in growth factor and cytokine receptor signaling pathways . J. Biol. Chem. . 275 . 49 . 38633–9 . 10993906 . 10.1074/jbc.M007849200. free .
22. July 2000 . Endo K, Takeshita T, Kasai H, Sasaki Y, Tanaka N, Asao H, Kikuchi K, Yamada M, Chenb M, O'Shea JJ, Sugamura K . STAM2, a new member of the STAM family, binding to the Janus kinases . FEBS Lett. . 477 . 1–2 . 55–61 . 10899310 . 10.1016/s0014-5793(00)01760-9. free .
23. March 2002 . Ueda T, Bruchovsky N, Sadar MD . Activation of the androgen receptor N-terminal domain by interleukin-6 via MAPK and STAT3 signal transduction pathways . J. Biol. Chem. . 277 . 9 . 7076–85 . 11751884 . 10.1074/jbc.M108255200. free .
24. August 2001 . Spiekermann K, Biethahn S, Wilde S, Hiddemann W, Alves F . Constitutive activation of STAT transcription factors in acute myelogenous leukemia . Eur. J. Haematol. . 67 . 2 . 63–71 . 11722592 . 10.1034/j.1600-0609.2001.t01-1-00385.x. 38074766 .
25. February 1997 . Fujitani Y, Hibi M, Fukada T, Takahashi-Tezuka M, Yoshida H, Yamaguchi T, Sugiyama K, Yamanaka Y, Nakajima K, Hirano T . An alternative pathway for STAT activation that is mediated by the direct interaction between JAK and STAT . Oncogene . 14 . 7 . 751–61 . 9047382 . 10.1038/sj.onc.1200907. free .
26. March 1998 . Guo D, Dunbar JD, Yang CH, Pfeffer LM, Donner DB . Induction of Jak/STAT signaling by activation of the type 1 TNF receptor . J. Immunol. . 160 . 6 . 2742–50 . 10.4049/jimmunol.160.6.2742 . 9510175 . free .
27. January 2002 . Miscia S, Marchisio M, Grilli A, Di Valerio V, Centurione L, Sabatino G, Garaci F, Zauli G, Bonvini E, Di Baldassarre A . Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells . Cell Growth Differ. . 13 . 1 . 13–8 . 11801527 .